Dynamic Coupling at the Ångström Scale

While momentum transfer from active particles to their immediate surroundings has been studied for both synthetic and biological micron‐scale systems, a similar phenomenon was presumed unlikely to exist at smaller length scales due to the dominance of viscosity in the ultralow Reynolds number regime. Using diffusion NMR spectroscopy, we studied the motion of two passive tracers—tetramethylsilane and benzene—dissolved in an organic solution of active Grubbs catalyst. Significant enhancements in diffusion were observed for both the tracers and the catalyst as a function of reaction rate. A similar behavior was also observed for the enzyme urease in aqueous solution. Surprisingly, momentum transfer at the molecular scale closely resembles that reported for microscale systems and appears to be independent of swimming mechanism. Our work provides new insight into the role of active particles on advection and mixing at the Ångström scale.     

New designs for inhibitors of the NF-κB: DNA binding

We present a series of new inhibitors of the association between nuclear factor kappa B (NF-B) and the corresponding B site in DNA. They were designed using the lead compound 15-deoxy-^12,14 -prostaglandin J₂ (PGJ2), which is a natural product with demonstrated inhibitory efficiency for this system. First, the binding mode of PGJ2 to NF-B was unraveled by GOLD docking calculation. Subsequently, substitutions were made to PGJ2 to optimize its association with NF-B. Care was taken not to strongly increase the reactivity of the new compounds, and to keep the overall shape, size and hydrophilicity of the lead compound, which should render them a similar bioavailability. Molecular mechanics calculations were performed to decide on the suitability of the substitutions, and to evaluate the energies of association with NF-B. Density functional theory calculations were performed also to study the overall reactivity of the substituted drugs towards NF-B. Important general conclusions were obtained, concerning the improvement of these natural inhibitors; namely, a set of rational methodologies were deduced to improve the association between the PGJ2 derivatives and NF-B, and their efficiency demonstrated by generating a set of substituted complexes, some of them with a very much increased affinity for NF-B, opening new doors to enlarge the therapeutic capabilities of this class of drugs.     

Influence of structure and solubility of chain transfer agents on the RAFT control of dispersion polymerisation in scCO2

Reversible addition–fragmentation chain transfer (RAFT) dispersion polymerisation of methyl methacrylate (MMA) is performed in supercritical carbon dioxide (scCO₂) with 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) present as chain transfer agent (CTA) and surprisingly shows good control over PMMA molecular weight. Kinetic studies of the polymerisation in scCO₂ also confirm these data. By contrast, only poor control of MMA polymerisation is obtained in toluene solution, as would be expected for this CTA which is better suited for acrylates. In this regard, we select a range of CTAs and use them to determine the parameters that must be considered for good control in dispersion polymerisation in scCO₂. A thorough investigation of the nucleation stage during the dispersion polymerisation reveals an unexpected “in situ two-stage” mechanism that strongly determines how the CTA works. Finally, using a novel computational solvation model, we identify a correlation between polymerisation control and degree of solubility of the CTAs. All of this ultimately gives rise to a simple, elegant and counterintuitive guideline to select the best CTA for RAFT dispersion polymerisation in scCO₂.

RAFT dispersion polymerisation of methyl methacrylate is performed in scCO₂ with 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) present as chain transfer agent (CTA) and surprisingly shows good control over PMMA molecular weight.     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.     

Optimization methodology assessment for the inlet velocity profile of a hydraulic turbine draft tube: part II—performance evaluation of draft tube model

Computational Fluids Dynamics (CFD) tools guide engineers and designers to estimate the performance of new designs. However, a CFD analysis can be very time-consuming depending mainly on the grid size and domain complexity. Thus, this paper aims to describe the tools used to evaluate and compare the performance of different 3D draft tube models for reducing the time-effort needed in an optimization procedure. The results presented here, are the second part of an overall research to establish a global optimization methodology to improve the performance of an hydraulic draft tube through the inlet velocity profile. Previously, three steps of optimization methodology to minimize the energy losses were studied: the inlet velocity profile parameterization, the numerical optimization set-up and the objective function validation. In the latter step, a global optimization method called Multi Island Genetic Algorithm (MIGA) was considered, which requires a large number of iterations before producing a reliable result. This step is able to identify an efficient inlet velocity profile to minimize the energy losses through the draft tube model. However, each iteration is expensive in terms of computational time due to the need for 3D Navier–Stokes (NS) computations to evaluate each profile’s fitness. Thus, in this work the methodology attempts to accelerate the optimization process with accurate results. In order to achieve the goal, the grid size of the 3D draft tube model was minimized, resulting in a much lower computational cost. Specifically, the draft tube calculations were performed on a sequence of five different grids each having approximately twice the number of elements compared to the previous. The measurements of the sensitivity of the draft tube performance quantities to the change of the inlet velocity parameters during the process showed that, in spite of the numerical difference between its performance, the results have the same tendency. Consequently, the 3D draft tube numerical model with a minimal grid size, is reliable and left record of its capabilities for being integrated in the optimization process.     

Optimizing routes and stock

This work is motivated by a problem proposed to the authors by a bakery company in Northern Spain. The objective is to design the daily routes over the week in order to minimize the total traveled distance. For reducing this total distance, some flexibility in the dates of delivery is introduced, which will cause a stock. Therefore, we study the problem under the bi-objective perspective, “minimizing” simultaneously the total traveled distance and the stock. A bi-objective mixed-integer linear model for the problem is formulated and two methodologies of solution are presented. The first one is based on a series of linked variable neighborhood searches and the second one is based on NSGA-II provided of specific operators. Numerical results showing the obtained estimated Pareto front in both cases are presented.     

Optimizing vehicle routes in a bakery company allowing flexibility in delivery dates

The work addressed in this paper is motivated from a real problem proposed to the authors by a bakery company in Northern Spain. The objective is to minimize the total distance travelled for the daily routes over the week. In order to reduce this total distance, some flexibility in the dates of delivery is introduced. A mixed-integer linear model for the problem is formulated. In addition, a two-phase method based in GRASP and path-relinking metaheuristic strategies is proposed. Computational experiments show that the method performs very well, obtaining high-quality solutions in short computational times. Moreover, when it is applied to real-data-based instances, the obtained solutions considerably reduce transportation costs over the planning horizon.     

Picard Iterations for Diffusions on Symmetric Matrices

Matrix-valued stochastic processes have been of significant importance in areas such as physics, engineering and mathematical finance. One of the first models studied has been the so-called Wishart process, which is described as the solution of a stochastic differential equation in the space of matrices. In this paper, we analyze natural extensions of this model and prove the existence and uniqueness of the solution. We do this by carrying out a Picard iteration technique in the space of symmetric matrices. This approach takes into account the operator character of the matrices, which helps to corroborate how the Lipchitz conditions also arise naturally in this context.     

Bianchi–Bäcklund transforms and dressing actions,revisited

We characterize Bianchi–Bäcklund transformations of surfaces of positive constant Gauss curvature in terms of dressing actions of the simplest type on the space of harmonic maps.